Disease relevance of Tnfrsf17

• TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS [1].
• The BCMA gene is a new gene discovered by the molecular analysis of a t(4;16) translocation, characteristic of a human T cell lymphoma [2].
• Mice with severe combined immunodeficiency syndrome (SCID) exhibit an impairment in both T and B cell maturation, whereas myelopoiesis remains unaffected [3].
• CTLA4Ig inhibits T cell-dependent B-cell maturation in murine systemic lupus erythematosus [4].
• These data suggest that CP96,345 inhibits granuloma IgM secretion by blocking intragranuloma B cell maturation at a terminal stage of B cell differentiation [5].

High impact information on Tnfrsf17

• Death by apoptosis is characteristic of cells undergoing deletion during embryonic development, T- and B-cell maturation and endocrine-induced atrophy [6].
• Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation [7].
• An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway [8].
• A mouse mutant that lacks most of the Ig-alpha cytoplasmic tail exhibits only a small impairment in early B cell development but a severe block in the generation of the peripheral B cell pool, revealing a checkpoint in B cell maturation that ensures the expression of a functional BCR on mature B cells [9].
• The blocks in osteoclast and B-cell maturation were unexpected [10].

Chemical compound and disease context of Tnfrsf17

• Malignant lymphomas were induced in Swiss mice treated intragastrically with methyl-2-benzimidazole carbamate (MBC, BCM, Carbendazim) and given sodium nitrite in their drinking water [11].
• Maturation to immunoglobulin secretion induced by the mycoplasma alone was low compared with induction by lipopolysaccharide (LPS), but could reach the same levels achieved with LPS by the addition of a B-cell maturation factor obtained from lectin-activated EL-4 thymoma cells [12].

Biological context of Tnfrsf17

• B cell maturation antigen, the receptor for a proliferation-inducing ligand and B cell-activating factor of the TNF family, induces antigen presentation in B cells [13].
• BCMA binds two TNF family members, BAFF and APRIL, that stimulate cellular proliferation [14].
• In the DKO mice, B cell maturation was blocked at the transitional type 1 (T1) stage and B cells were prone to apoptosis, in common with BASH-deficient mice [15].
• B cells lacking RelB are defective in proliferative responses, but undergo normal B cell maturation to Ig secretion and Ig class switching [16].
• We conclude that Bcmd is expressed in bone marrow cells, most likely B cells, where it hinders short-lived B cell maturation to a long-lived phenotype with the potential to form memory B cells [17].

Anatomical context of Tnfrsf17

• In contrast, mice lacking BCMA had normal-appearing B lymphocyte compartments [8].
• Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA-/- mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls [18].
• BCMA is essential for the survival of long-lived bone marrow plasma cells [18].
• We have inactivated BCMA in the mouse germ line [14].
• The cellular interactions between T and HK cells and cytokine production suggest that activated T cells not only stimulate resting B cells directly, but also support B cell maturation indirectly by stimulating the development of FDC [19].

Associations of Tnfrsf17 with chemical compounds

• The tumor necrosis factor (TNF)-related ligand B lymphocyte stimulator (BLyS) binds two TNF receptor family members, transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI) and B cell maturation molecule (BCMA) [20].
• We conclude that arginine deficiency impairs early B cell maturation [21].
• In this study, by generating transgenic mice expressing truncated Ii lacking its luminal domain, we could dissect the chaperonin activity of Ii from its role in B cell maturation [22].
• In the present studies murine B cell maturation was used as a model system to examine and compare the effects of TCDD and dexamethasone on cell function [23].
• B lymphocyte differentiation induced by lipopolysaccharide. III. Suppression of B cell maturation by anti-mouse immunoglobulin antibodies [24].

Physical interactions of Tnfrsf17

• Moreover, we show that, in contrast to monovalent BAFF-R-Fc, monovalent BCMA does not form stable complexes with BAFF [25].
• The analysis of the two types of gamma 2b transgenic mice shows that the signals for preB cell development are highly complex and promises to reveal new insights into the molecular and cellular mechanisms of B cell maturation [26].

Regulatory relationships of Tnfrsf17

• Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation [27].
• Moreover, SP receptor antagonist affects a variety of cytokine circuits that could influence IgM B cell maturation in vivo [5].
• We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells [28].
• Thus, in the presence of this antibody, even Th1 SN stimulate B cell maturation maximally [29].
• BMF-T from S26.5 supernatant was separated from IFN-gamma and BCGF-II and was shown to induce B cell maturation without affecting B cell proliferation [30].

Other interactions of Tnfrsf17

• Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival [18].
• Double knockout mice show BASH and PKCdelta have different epistatic relationships in B cell maturation and CD40-mediated activation [15].
• NF-kappaB2/p100 cleavage was abrogated in B cells from A/WySnJ mice possessing a mutant BR3 gene, but not in TACI or BCMA null B cells [31].
• RelB, another member of the NF-kappa B/Rel family of transcription factors, is expressed during the latter stages of B cell maturation and can bind to regulatory sites within the Ig heavy chain locus [16].
• These findings (taken in conjunction with the previously described immune defects in CBA/N mice and other studies of B-cell maturation) suggest to us that Lyb3 is a cell surface component expressed selectively on a mature B-cell subclass [32].

Analytical, diagnostic and therapeutic context of Tnfrsf17

• Demonstration of B-cell maturation in X-linked immunodeficient mice by simultaneous three-colour immunofluorescence [33].
• These data describe a novel animal model for NK cell-induced B cell maturation to Ig secretion and suggest a pathway for Ig production in response to T1-2 Ag [34].
• To evaluate the processes that maintain normoglycemia and regulate BCM during pancreatic regeneration, C57BL/6 mice were analyzed for 15 days following 60% partial pancreatectomy (Px) [35].
• The effect of fractionated total lymphoid irradiation (TLI) on the induction of cells blocking in vivo B cell maturation was examined [36].
• CONCLUSIONS: The mechanism of prolonged xenograft survival in this model may include inhibition of antibody production by arrest of B-cell maturation during development from IgM(dull)/IgD(bright) mature B cells to antibody producing cells, and inhibition of T cell activation [37].

References